Comprehensive mapping of the human brain epigenome by researchers has uncovered large-scale changes that take place during the formation of brain circuitry. The ground-breaking research offers an unprecedented view of the epigenome during brain development.

High-resolution mapping of the epigenome has discovered unique patterns that emerge during the generation of brain circuitry in childhood.

While the ‘genome’ can be thought of as the instruction manual that contains the blueprints or genes for all of the components of our cells and our body, the ‘epigenome’ is an additional layer of information on top of the genes that changes the way they are used.

The new insights provide the foundation for investigating the role the epigenome plays in learning, memory formation, brain structure and mental illness, the scientists say.

Joseph R Ecker, senior author of the study and director of the genomic analysis laboratory at California’s Salk Institute for Biological Studies in California, says the research shows that the period during which the neural circuits of the brain mature is accompanied by a parallel process of large-scale reconfiguration of the neural epigenome.

A healthy brain is the product of a long period of developmental processes, Ecker says. These periods of development forge complex structures and connections within our brains. The front part of our brain, called the frontal cortex, is critical for our abilities to think, decide and act.

The frontal cortex is made up of distinct types of cells, such as neurons and glia, which each perform very different functions.

But while we know these distinct types of cells in the brain all contain the same genome sequence – the A, C, G and T ‘letters’ of the DNA code that provides the instructions to build the cell – the question is: How can they each have such different identities?

Ecker says the answer lies in a secondary layer of information written on top of the DNA of the genome, referred to as the ‘epigenome’. One component of the epigenome, called DNA methylation, consists of small chemical tags that are placed upon some of the C letters in the genome.

These tags alert the cell to treat the tagged DNA differently and change the way it is read; for example, causing a nearby gene to be turned off. DNA methylation plays an essential role in our development and in our bodies’ ability to make and distinguish different cell types.

To better understand the role of the epigenome in brain development, the scientists used advanced DNA sequencing technologies to produce comprehensive maps of precisely which Cs in the genome have these chemical tags, in brains from infants through to adults.

The study gives the first comprehensive maps of DNA methylation and its dynamics in the brain throughout the lifespan of both humans and mice.

The researchers discovered that a unique type of DNA methylation emerges precisely when the neurons in a child’s developing brain are forming new connections with one another; essentially when critical brain circuitry is being formed.

This unique form of DNA methylation is almost exclusively found in neurons, and in patterns that are very similar between individuals. The research shows that a highly ordered system of DNA tagging operates in brain cells and that this system is unique to the brain.

Recent studies have suggested that DNA methylation may be involved in mental illnesses, including bipolar disorder, depression and schizophrenia. Environmental or experience-dependent alteration of these unique patterns of DNA methylation in neurons could lead to changes in gene expression.

The alterations of these methylation patterns will change the way networks are formed, which could, in turn, lead to the appearance of mental disorders later in life.

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